scholarly journals Impact of Zinc- or Copper-Doped Mesoporous Bioactive Glass Nanoparticles on the Osteogenic Differentiation and Matrix Formation of Mesenchymal Stromal Cells

Materials ◽  
2021 ◽  
Vol 14 (8) ◽  
pp. 1864
Author(s):  
Fabian Westhauser ◽  
Simon Decker ◽  
Qaisar Nawaz ◽  
Felix Rehder ◽  
Sebastian Wilkesmann ◽  
...  
Keyword(s):  
Bioactive Glass ◽  
Osteogenic Differentiation ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Related Gene ◽  
Future Studies ◽  
Positive Effects ◽  
Expression Of Genes ◽  
Genes Encoding ◽  
Mesoporous Bioactive Glass

Mesoporous bioactive glass nanoparticles (MBGNs) have gained relevance in bone tissue engineering, especially since they can be used as vectors for therapeutically active ions like zinc (Zn) or copper (Cu). In this study, the osteogenic properties of the ionic dissolution products (IDPs) of undoped MBGNs (composition in mol%: 70 SiO2, 30 CaO) and MBGNs doped with 5 mol% of either Zn (5Zn-MBGNs) or Cu (5Cu-MBGNs; compositions in mol%: 70 SiO2, 25 CaO, 5 ZnO/CuO) on human bone marrow-derived mesenchymal stromal cells were evaluated. Extracellular matrix (ECM) formation and calcification were assessed, as well as the IDPs’ influence on viability, cellular osteogenic differentiation and the expression of genes encoding for relevant members of the ECM. The IDPs of undoped MBGNs and 5Zn-MBGNs had a comparable influence on cell viability, while it was enhanced by IDPs of 5Cu-MBGNs compared to the other MBGNs. IDPs of 5Cu-MBGNs had slightly positive effects on ECM formation and calcification. 5Zn-MBGNs provided the most favorable pro-osteogenic properties since they increased not only cellular osteogenic differentiation and ECM-related gene expression but also ECM formation and calcification significantly. Future studies should analyze other relevant properties of MBGNs, such as their impact on angiogenesis.

scholarly journals Bioactive Glass (BG) ICIE16 Shows Promising Osteogenic Properties Compared to Crystallized 45S5-BG

2020 ◽  
Vol 21 (5) ◽  
pp. 1639 ◽  
Author(s):  
Fabian Westhauser ◽  
Frederike Hohenbild ◽  
Marcela Arango-Ospina ◽  
Sarah I. Schmitz ◽  
Sebastian Wilkesmann ◽  
...  
Keyword(s):  
Bioactive Glass ◽  
Osteogenic Differentiation ◽  
Stromal Cells ◽  
Biological Properties ◽  
Cellular Level ◽  
Human Mesenchymal Stromal Cells ◽  
Ecm Proteins ◽  
Genes Encoding ◽  
Increased Activity ◽  
Stimulation Of

The ICIE16-bioactive glass (BG) (48.0 SiO2, 6.6 Na2O, 32.9 CaO, 2.5 P2O5, 10.0 K2O (wt %)) has been developed as an alternative to 45S5-BG, the original BG composition (45.0 SiO2, 24.5 Na2O, 24.5 CaO, 6.0 P2O5 (wt %)), with the intention of broadening the BG sintering window while maintaining bioactivity. Because there is a lack of reports on ICIE16-BG biological properties, the influence of ICIE16-BG on viability, proliferation, and osteogenic differentiation of human mesenchymal stromal cells (MSCs) was evaluated in direct comparison to 45S5-BG in this study. The BGs underwent heat treatment similar to that which is required in order to fabricate scaffolds by sintering, which resulted in crystallization of 45S5-BG (45S5-CBG) while ICIE16 remained amorphous. Granules based on both BGs were biocompatible, but ICIE16-BG was less harmful to cell viability, most likely due to a more pronounced pH alkalization in the 45S5-CBG group. ICIE16-BG outperformed 45S5-CBG in terms of osteogenic differentiation at the cellular level, as determined by the increased activity of alkaline phosphatase. However, granules from both BGs were comparable regarding the stimulation of expression levels of genes encoding for osseous extracellular matrix (ECM) proteins. The addition of therapeutically active ions to ICIE16-BG might further improve its ability to stimulate ECM production and should be investigated in upcoming studies.

Effects of hypoxia on osteogenic differentiation of mesenchymal stromal cells used as a cell therapy for avascular necrosis of the femoral head

Cytotherapy ◽  
2016 ◽  
Vol 18 (9) ◽  
pp. 1087-1099 ◽  
Author(s):  
Gabriela Ciapetti ◽  
Donatella Granchi ◽  
Caterina Fotia ◽  
Lucia Savarino ◽  
Dante Dallari ◽  
...  
Keyword(s):  
Femoral Head ◽  
Cell Therapy ◽  
Osteogenic Differentiation ◽  
Avascular Necrosis ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
A Cell

scholarly journals Alterations of mesenchymal stromal cells in cerebrospinal fluid: insights from transcriptomics and an ALS clinical trial

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Ashley A. Krull ◽  
Deborah O. Setter ◽  
Tania F. Gendron ◽  
Sybil C. L. Hrstka ◽  
Michael J. Polzin ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cerebrospinal Fluid ◽  
Growth Factors ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Large Scale ◽  
Therapeutic Benefit ◽  
Protein Levels ◽  
Genes Encoding ◽  
Intrathecal Space

Abstract Background Mesenchymal stromal cells (MSCs) have been studied with increasing intensity as clinicians and researchers strive to understand the ability of MSCs to modulate disease progression and promote tissue regeneration. As MSCs are used for diverse applications, it is important to appreciate how specific physiological environments may stimulate changes that alter the phenotype of the cells. One need for neuroregenerative applications is to characterize the spectrum of MSC responses to the cerebrospinal fluid (CSF) environment after their injection into the intrathecal space. Mechanistic understanding of cellular biology in response to the CSF environment may predict the ability of MSCs to promote injury repair or provide neuroprotection in neurodegenerative diseases. Methods In this study, we characterized changes in morphology, metabolism, and gene expression occurring in human adipose-derived MSCs cultured in human (hCSF) or artificial CSF (aCSF) as well as examined relevant protein levels in the CSF of subjects treated with MSCs for amyotrophic lateral sclerosis (ALS). Results Our results demonstrated that, under intrathecal-like conditions, MSCs retained their morphology, though they became quiescent. Large-scale transcriptomic analysis of MSCs revealed a distinct gene expression profile for cells cultured in aCSF. The aCSF culture environment induced expression of genes related to angiogenesis and immunomodulation. In addition, MSCs in aCSF expressed genes encoding nutritional growth factors to expression levels at or above those of control cells. Furthermore, we observed a dose-dependent increase in growth factors and immunomodulatory cytokines in CSF from subjects with ALS treated intrathecally with autologous MSCs. Conclusions Overall, our results suggest that MSCs injected into the intrathecal space in ongoing clinical trials remain viable and may provide a therapeutic benefit to patients.

Ions release behavior of vanadium-doped mesoporous bioactive glass particles and effect on BMSCs osteogenic differentiation via FAK/MAPK signaling pathway

2021 ◽  
Author(s):  
Jiangfeng Li ◽  
Junying Li ◽  
Yuhao Wei ◽  
Na Xu ◽  
Jingtao Li ◽  
...  
Keyword(s):  
Bone Formation ◽  
Bioactive Glass ◽  
Osteogenic Differentiation ◽  
Bone Growth ◽  
Mapk Signaling ◽  
Release Behavior ◽  
Pentavalent Vanadium ◽  
Important Trace Element ◽  
Vanadium Ions ◽  
Mesoporous Bioactive Glass

Vanadium is an important trace element in bone to involve in bone metabolism, bone formation, and bone growth, but roles of various vanadium ions, especially pentavalent vanadium, in bone tissue...

scholarly journals The oncometabolite R-2-hydroxyglutarate dysregulates the differentiation of human mesenchymal stromal cells via inducing DNA hypermethylation

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Lizhen Liu ◽  
Kaimin Hu ◽  
Jingjing Feng ◽  
Huafang Wang ◽  
Shan Fu ◽  
...  
Keyword(s):  
Osteogenic Differentiation ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Chondrogenic Differentiation ◽  
Cell Counting ◽  
Human Mscs ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Dna Hypermethylation ◽  
Cartilaginous Tumors

Abstract Background Isocitrate dehydrogenase (IDH1/2) gene mutations are the most frequently observed mutations in cartilaginous tumors. The mutant IDH causes elevation in the levels of R-enantiomer of 2-hydroxylglutarate (R-2HG). Mesenchymal stromal cells (MSCs) are reasonable precursor cell candidates of cartilaginous tumors. This study aimed to investigate the effect of oncometabolite R-2HG on MSCs. Methods Human bone marrow MSCs treated with or without R-2HG at concentrations 0.1 to 1.5 mM were used for experiments. Cell Counting Kit-8 was used to detect the proliferation of MSCs. To determine the effects of R-2HG on MSC differentiation, cells were cultured in osteogenic, chondrogenic and adipogenic medium. Specific staining approaches were performed and differentiation-related genes were quantified. Furthermore, DNA methylation status was explored by Illumina array-based arrays. Real-time PCR was applied to examine the signaling component mRNAs involved in. Results R-2HG showed no influence on the proliferation of human MSCs. R-2HG blocked osteogenic differentiation, whereas promoted adipogenic differentiation of MSCs in a dose-dependent manner. R-2HG inhibited chondrogenic differentiation of MSCs, but increased the expression of genes related to chondrocyte hypertrophy in a lower concentration (1.0 mM). Moreover, R-2HG induced a pronounced DNA hypermethylation state of MSC. R-2HG also improved promotor methylation of lineage-specific genes during osteogenic and chondrogenic differentiation. In addition, R-2HG induced hypermethylation and decreased the mRNA levels of SHH, GLI1and GLI2, indicating Sonic Hedgehog (Shh) signaling inhibition. Conclusions The oncometabolite R-2HG dysregulated the chondrogenic and osteogenic differentiation of MSCs possibly via induction of DNA hypermethylation, improving the role of R-2HG in cartilaginous tumor development.

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